The ultimate goal of this investigative program is for Dr. Torgan to acquire knowledge and develop skills and interests that she can carry into an independent investigative career. The training program will permit Dr. Torgan exposure to a number of varied laboratory environments and techniques and should allow for the ready achievement of the ultimate goal of this proposal. When muscles are subjected to chronic exercise there results a change in the protein constituents of the muscle cell that are, for the most part, the result of switches in the use of specific genes and genetic programs. Little is known about how the muscle cell senses a need to alter its phenotype and how the initial signal is transduced to the nucleus to ultimately result in alterations in the use of specific genes. This work seeks to lay the groundwork for studies of the molecular signaling events that underlie the phenotypic plasticity of skeletal muscles in response to exercise conditioning. These overall concerns and goals will be approached with the following Specific Aims: the stable transfection of muscle cell lines, the development of a nerve-muscle co-culture system and the study the effects of non-myocyte conditioned media on myocyte differentiation and expression of target proteins, the cloning of the rabbit skeletal muscle adenylyl cyclase cDNA, and the development and use of systems that will allow controlled stretch and membrane deformation of skeletal myotubes in vitro. Rather than targeting one particular neuromuscular disease, this proposal is targeted toward gaining further insight into the importance of neural input and activity to muscle phenotype and function. Not only are such studies important to basic research of the etiology of any one of a number of neuromuscular diseases, but better understanding of the cellular mechanisms responsible for the response of muscles to chronic exercise will provide important therapeutic insights directed toward the effective treatment of such diseases.